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Sabine Vaur - One of the best experts on this subject based on the ideXlab platform.
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a second wpl1 anti cohesion pathway requires dephosphorylation of fission yeast kleisin rad21 by pp4
The EMBO Journal, 2017Co-Authors: Adrien Birot, Jean-paul Javerzat, Karen Eguienta, Stéphanie Vazquez, Karl Ekwall, Stéphane Claverol, Marc Bonneu, Sabine VaurAbstract:Abstract Cohesin mediates sister chromatid cohesion which is essential for chromosome segregation and repair. Sister chromatid cohesion requires an acetyl‐transferase (Eso1 in fission yeast) counteracting Wpl1, promoting Cohesin release from DNA. We report here that Wpl1 anti‐cohesion function includes an additional mechanism. A genetic screen uncovered that Protein Phosphatase 4 (PP4) mutants allowed cell survival in the complete absence of Eso1. PP4 co‐immunoprecipitated Wpl1 and Cohesin and Wpl1 triggered Rad21 de‐phosphorylation in a PP4‐dependent manner. Relevant residues were identified and mapped within the central domain of Rad21. Phospho‐mimicking alleles dampened Wpl1 anti‐cohesion activity, while alanine mutants were neutral indicating that Rad21 phosphorylation would shelter Cohesin from Wpl1 unless erased by PP4. Experiments in post‐replicative cells lacking Eso1 revealed two Cohesin populations. Type 1 was released from DNA by Wpl1 in a PP4‐independent manner. Type 2 Cohesin, however, remained DNA‐bound and lost its cohesiveness in a manner depending on Wpl1‐ and PP4‐mediated Rad21 de‐phosphorylation. These results reveal that Wpl1 antagonizes sister chromatid cohesion by a novel pathway regulated by the phosphorylation status of the Cohesin kleisin subunit.
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A second Wpl1 anti‐cohesion pathway requires dephosphorylation of fission yeast kleisin Rad21 by PP4
The EMBO journal, 2017Co-Authors: Adrien Birot, Jean-paul Javerzat, Karen Eguienta, Stéphanie Vazquez, Karl Ekwall, Stéphane Claverol, Marc Bonneu, Sabine VaurAbstract:Abstract Cohesin mediates sister chromatid cohesion which is essential for chromosome segregation and repair. Sister chromatid cohesion requires an acetyl‐transferase (Eso1 in fission yeast) counteracting Wpl1, promoting Cohesin release from DNA. We report here that Wpl1 anti‐cohesion function includes an additional mechanism. A genetic screen uncovered that Protein Phosphatase 4 (PP4) mutants allowed cell survival in the complete absence of Eso1. PP4 co‐immunoprecipitated Wpl1 and Cohesin and Wpl1 triggered Rad21 de‐phosphorylation in a PP4‐dependent manner. Relevant residues were identified and mapped within the central domain of Rad21. Phospho‐mimicking alleles dampened Wpl1 anti‐cohesion activity, while alanine mutants were neutral indicating that Rad21 phosphorylation would shelter Cohesin from Wpl1 unless erased by PP4. Experiments in post‐replicative cells lacking Eso1 revealed two Cohesin populations. Type 1 was released from DNA by Wpl1 in a PP4‐independent manner. Type 2 Cohesin, however, remained DNA‐bound and lost its cohesiveness in a manner depending on Wpl1‐ and PP4‐mediated Rad21 de‐phosphorylation. These results reveal that Wpl1 antagonizes sister chromatid cohesion by a novel pathway regulated by the phosphorylation status of the Cohesin kleisin subunit.
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A second Wpl1 anti‐cohesion pathway requires dephosphorylation of fission yeast kleisin Rad21 by PP 4
EMBO Journal, 2017Co-Authors: Adrien Birot, Jean-paul Javerzat, Karen Eguienta, Sabine Vaur, Stéphanie Vazquez, Karl Ekwall, Stéphane Claverol, Marc Bonneu, Jean‐paul JaverzatAbstract:Cohesin mediates sister chromatid cohesion which is essential for chromosome segregation and repair. Sister chromatid cohesion requires an acetyl-transferase (Eso1 in fission yeast) counteracting Wpl1, promoting Cohesin release from DNA We report here that Wpl1 anti-cohesion function includes an additional mechanism. A genetic screen uncovered that Protein Phosphatase 4 (PP4) mutants allowed cell survival in the complete absence of Eso1. PP4 co-immunoprecipitated Wpl1 and Cohesin and Wpl1 triggered Rad21 de-phosphorylation in a PP4-dependent manner. Relevant residues were identified and mapped within the central domain of Rad21. Phospho-mimicking alleles dampened Wpl1 anti-cohesion activity, while alanine mutants were neutral indicating that Rad21 phosphorylation would shelter Cohesin from Wpl1 unless erased by PP4. Experiments in post-replicative cells lacking Eso1 revealed two Cohesin populations. Type 1 was released from DNA by Wpl1 in a PP4-independent manner. Type 2 Cohesin, however, remained DNA-bound and lost its cohesiveness in a manner depending on Wpl1- and PP4-mediated Rad21 de-phosphorylation. These results reveal that Wpl1 antagonizes sister chromatid cohesion by a novel pathway regulated by the phosphorylation status of the Cohesin kleisin subunit.
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Pds5 promotes Cohesin acetylation and stable Cohesin–chromosome interaction
EMBO reports, 2012Co-Authors: Sabine Vaur, Stéphanie Vazquez, Amélie Feytout, Jean-paul JaverzatAbstract:Pds5 and Wpl1 act as anti-establishment factors preventing sister-chromatid cohesion until counteracted in S-phase by the Cohesin acetyl-transferase Eso1. However, Pds5 is also required to maintain sister-chromatid cohesion in G2. Here, we show that Pds5 is essential for Cohesin acetylation by Eso1 and ensures the maintenance of cohesion by promoting a stable Cohesin interaction with replicated chromosomes. The latter requires Eso1 only in the presence of Wapl, indicating that Cohesin stabilization relies on Eso1 only to neutralize the anti-establishment activity. We suggest that Eso1 requires Pds5 to counteract anti-establishment. This allows both cohesion establishment and Pds5-dependent stable Cohesin binding to chromosomes.
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psm3 acetylation on conserved lysine residues is dispensable for viability in fission yeast but contributes to eso1 mediated sister chromatid cohesion by antagonizing wpl1
Molecular and Cellular Biology, 2011Co-Authors: Amélie Feytout, Sylvie Genier, Sabine Vaur, Stéphanie Vazquez, Jean-paul JaverzatAbstract:: In budding yeast and humans, cohesion establishment during S phase requires the acetyltransferase Eco1/Esco1-2, which acetylates the Cohesin subunit Smc3 on two conserved lysine residues. Whether Smc3 is the sole Eco1/Esco1-2 effector and how Smc3 acetylation promotes cohesion are unknown. In fission yeast (Schizosaccharomyces pombe), as in humans, Cohesin binding to G(1) chromosomes is dynamic and the unloading reaction is stimulated by Wpl1 (human ortholog, Wapl). During S phase, a subpopulation of Cohesin becomes stably bound to chromatin in an Eso1 (fission yeast Eco1/Esco1-2)-dependent manner. Cohesin stabilization occurs unevenly along chromosomes. Cohesin remains largely labile at the rDNA repeats but binds mostly in the stable mode to pericentromere regions. This pattern is largely unchanged in eso1Δ wpl1Δ cells, and cohesion is unaffected, indicating that the main Eso1 role is counteracting Wpl1. A mutant of Psm3 (fission yeast Smc3) that mimics its acetylated state renders Cohesin less sensitive to Wpl1-dependent unloading and partially bypasses the Eso1 requirement but cannot generate the stable mode of Cohesin binding in the absence of Eso1. Conversely, nonacetylatable Psm3 reduces the stable Cohesin fraction and affects cohesion in a Wpl1-dependent manner, but cells are viable. We propose that Psm3 acetylation contributes to Eso1 counteracting of Wpl1 to secure stable Cohesin interaction with postreplicative chromosomes but that it is not the sole molecular event by which this occurs.
Jean-paul Javerzat - One of the best experts on this subject based on the ideXlab platform.
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a second wpl1 anti cohesion pathway requires dephosphorylation of fission yeast kleisin rad21 by pp4
The EMBO Journal, 2017Co-Authors: Adrien Birot, Jean-paul Javerzat, Karen Eguienta, Stéphanie Vazquez, Karl Ekwall, Stéphane Claverol, Marc Bonneu, Sabine VaurAbstract:Abstract Cohesin mediates sister chromatid cohesion which is essential for chromosome segregation and repair. Sister chromatid cohesion requires an acetyl‐transferase (Eso1 in fission yeast) counteracting Wpl1, promoting Cohesin release from DNA. We report here that Wpl1 anti‐cohesion function includes an additional mechanism. A genetic screen uncovered that Protein Phosphatase 4 (PP4) mutants allowed cell survival in the complete absence of Eso1. PP4 co‐immunoprecipitated Wpl1 and Cohesin and Wpl1 triggered Rad21 de‐phosphorylation in a PP4‐dependent manner. Relevant residues were identified and mapped within the central domain of Rad21. Phospho‐mimicking alleles dampened Wpl1 anti‐cohesion activity, while alanine mutants were neutral indicating that Rad21 phosphorylation would shelter Cohesin from Wpl1 unless erased by PP4. Experiments in post‐replicative cells lacking Eso1 revealed two Cohesin populations. Type 1 was released from DNA by Wpl1 in a PP4‐independent manner. Type 2 Cohesin, however, remained DNA‐bound and lost its cohesiveness in a manner depending on Wpl1‐ and PP4‐mediated Rad21 de‐phosphorylation. These results reveal that Wpl1 antagonizes sister chromatid cohesion by a novel pathway regulated by the phosphorylation status of the Cohesin kleisin subunit.
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A second Wpl1 anti‐cohesion pathway requires dephosphorylation of fission yeast kleisin Rad21 by PP4
The EMBO journal, 2017Co-Authors: Adrien Birot, Jean-paul Javerzat, Karen Eguienta, Stéphanie Vazquez, Karl Ekwall, Stéphane Claverol, Marc Bonneu, Sabine VaurAbstract:Abstract Cohesin mediates sister chromatid cohesion which is essential for chromosome segregation and repair. Sister chromatid cohesion requires an acetyl‐transferase (Eso1 in fission yeast) counteracting Wpl1, promoting Cohesin release from DNA. We report here that Wpl1 anti‐cohesion function includes an additional mechanism. A genetic screen uncovered that Protein Phosphatase 4 (PP4) mutants allowed cell survival in the complete absence of Eso1. PP4 co‐immunoprecipitated Wpl1 and Cohesin and Wpl1 triggered Rad21 de‐phosphorylation in a PP4‐dependent manner. Relevant residues were identified and mapped within the central domain of Rad21. Phospho‐mimicking alleles dampened Wpl1 anti‐cohesion activity, while alanine mutants were neutral indicating that Rad21 phosphorylation would shelter Cohesin from Wpl1 unless erased by PP4. Experiments in post‐replicative cells lacking Eso1 revealed two Cohesin populations. Type 1 was released from DNA by Wpl1 in a PP4‐independent manner. Type 2 Cohesin, however, remained DNA‐bound and lost its cohesiveness in a manner depending on Wpl1‐ and PP4‐mediated Rad21 de‐phosphorylation. These results reveal that Wpl1 antagonizes sister chromatid cohesion by a novel pathway regulated by the phosphorylation status of the Cohesin kleisin subunit.
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A second Wpl1 anti‐cohesion pathway requires dephosphorylation of fission yeast kleisin Rad21 by PP 4
EMBO Journal, 2017Co-Authors: Adrien Birot, Jean-paul Javerzat, Karen Eguienta, Sabine Vaur, Stéphanie Vazquez, Karl Ekwall, Stéphane Claverol, Marc Bonneu, Jean‐paul JaverzatAbstract:Cohesin mediates sister chromatid cohesion which is essential for chromosome segregation and repair. Sister chromatid cohesion requires an acetyl-transferase (Eso1 in fission yeast) counteracting Wpl1, promoting Cohesin release from DNA We report here that Wpl1 anti-cohesion function includes an additional mechanism. A genetic screen uncovered that Protein Phosphatase 4 (PP4) mutants allowed cell survival in the complete absence of Eso1. PP4 co-immunoprecipitated Wpl1 and Cohesin and Wpl1 triggered Rad21 de-phosphorylation in a PP4-dependent manner. Relevant residues were identified and mapped within the central domain of Rad21. Phospho-mimicking alleles dampened Wpl1 anti-cohesion activity, while alanine mutants were neutral indicating that Rad21 phosphorylation would shelter Cohesin from Wpl1 unless erased by PP4. Experiments in post-replicative cells lacking Eso1 revealed two Cohesin populations. Type 1 was released from DNA by Wpl1 in a PP4-independent manner. Type 2 Cohesin, however, remained DNA-bound and lost its cohesiveness in a manner depending on Wpl1- and PP4-mediated Rad21 de-phosphorylation. These results reveal that Wpl1 antagonizes sister chromatid cohesion by a novel pathway regulated by the phosphorylation status of the Cohesin kleisin subunit.
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Pds5 promotes Cohesin acetylation and stable Cohesin–chromosome interaction
EMBO reports, 2012Co-Authors: Sabine Vaur, Stéphanie Vazquez, Amélie Feytout, Jean-paul JaverzatAbstract:Pds5 and Wpl1 act as anti-establishment factors preventing sister-chromatid cohesion until counteracted in S-phase by the Cohesin acetyl-transferase Eso1. However, Pds5 is also required to maintain sister-chromatid cohesion in G2. Here, we show that Pds5 is essential for Cohesin acetylation by Eso1 and ensures the maintenance of cohesion by promoting a stable Cohesin interaction with replicated chromosomes. The latter requires Eso1 only in the presence of Wapl, indicating that Cohesin stabilization relies on Eso1 only to neutralize the anti-establishment activity. We suggest that Eso1 requires Pds5 to counteract anti-establishment. This allows both cohesion establishment and Pds5-dependent stable Cohesin binding to chromosomes.
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psm3 acetylation on conserved lysine residues is dispensable for viability in fission yeast but contributes to eso1 mediated sister chromatid cohesion by antagonizing wpl1
Molecular and Cellular Biology, 2011Co-Authors: Amélie Feytout, Sylvie Genier, Sabine Vaur, Stéphanie Vazquez, Jean-paul JaverzatAbstract:: In budding yeast and humans, cohesion establishment during S phase requires the acetyltransferase Eco1/Esco1-2, which acetylates the Cohesin subunit Smc3 on two conserved lysine residues. Whether Smc3 is the sole Eco1/Esco1-2 effector and how Smc3 acetylation promotes cohesion are unknown. In fission yeast (Schizosaccharomyces pombe), as in humans, Cohesin binding to G(1) chromosomes is dynamic and the unloading reaction is stimulated by Wpl1 (human ortholog, Wapl). During S phase, a subpopulation of Cohesin becomes stably bound to chromatin in an Eso1 (fission yeast Eco1/Esco1-2)-dependent manner. Cohesin stabilization occurs unevenly along chromosomes. Cohesin remains largely labile at the rDNA repeats but binds mostly in the stable mode to pericentromere regions. This pattern is largely unchanged in eso1Δ wpl1Δ cells, and cohesion is unaffected, indicating that the main Eso1 role is counteracting Wpl1. A mutant of Psm3 (fission yeast Smc3) that mimics its acetylated state renders Cohesin less sensitive to Wpl1-dependent unloading and partially bypasses the Eso1 requirement but cannot generate the stable mode of Cohesin binding in the absence of Eso1. Conversely, nonacetylatable Psm3 reduces the stable Cohesin fraction and affects cohesion in a Wpl1-dependent manner, but cells are viable. We propose that Psm3 acetylation contributes to Eso1 counteracting of Wpl1 to secure stable Cohesin interaction with postreplicative chromosomes but that it is not the sole molecular event by which this occurs.
Jan-michael Peters - One of the best experts on this subject based on the ideXlab platform.
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wapl releases scc1 Cohesin and regulates chromosome structure and segregation in mouse oocytes
Journal of Cell Biology, 2020Co-Authors: Mariana C C Silva, Jan-michael Peters, Sean Powell, Sabrina Ladstatter, Johanna Gassler, Roman R Stocsits, Antonio Tedeschi, Kikue TachibanaAbstract:Cohesin is essential for genome folding and inheritance. In somatic cells, these functions are both mediated by Scc1-Cohesin, which in mitosis is released from chromosomes by Wapl and separase. In mammalian oocytes, cohesion is mediated by Rec8-Cohesin. Scc1 is expressed but neither required nor sufficient for cohesion, and its function remains unknown. Likewise, it is unknown whether Wapl regulates one or both Cohesin complexes and chromosome segregation in mature oocytes. Here, we show that Wapl is required for accurate meiosis I chromosome segregation, predominantly releases Scc1-Cohesin from chromosomes, and promotes production of euploid eggs. Using single-nucleus Hi-C, we found that Scc1 is essential for chromosome organization in oocytes. Increasing Scc1 residence time on chromosomes by Wapl depletion leads to vermicelli formation and intra-loop structures but, unlike in somatic cells, does not increase loop size. We conclude that distinct Cohesin complexes generate loops and cohesion in oocytes and propose that the same principle applies to all cell types and species.
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Cohesin’s ATPase Activity Couples Cohesin Loading onto DNA with Smc3 Acetylation
Current biology : CB, 2014Co-Authors: Rene Ladurner, Emanuel Kreidl, Venugopal Bhaskara, Pim J Huis In 't Veld, Iain F. Davidson, Georg Petzold, Jan-michael PetersAbstract:Summary Background Cohesin mediates sister chromatid cohesion by topologically entrapping sister DNA molecules inside its ring structure. Cohesin is loaded onto DNA by the Scc2/NIPBL-Scc4/MAU2-loading complex in a manner that depends on the adenosine triphosphatase (ATPase) activity of Cohesin's Smc1 and Smc3 subunits. Subsequent cohesion establishment during DNA replication depends on Smc3 acetylation by Esco1 and Esco2 and on recruitment of sororin, which "locks" Cohesin on DNA by inactivating the Cohesin release factor Wapl. Results Human Cohesin ATPase mutants associate transiently with DNA in a manner that depends on the loading complex but cannot be stabilized on chromatin by depletion of Wapl. These mutants cannot be acetylated, fail to interact with sororin, and do not mediate cohesion. The absence of Smc3 acetylation in the ATPase mutants is not a consequence of their transient association with DNA but is directly caused by their inability to hydrolyze ATP because acetylation of wild-type Cohesin also depends on ATP hydrolysis. Conclusions Our data indicate that cohesion establishment involves the following steps. First, Cohesin transiently associates with DNA in a manner that depends on the loading complex. Subsequently, ATP hydrolysis by Cohesin leads to entrapment of DNA and converts Smc3 into a state that can be acetylated. Finally, Smc3 acetylation leads to recruitment of sororin, inhibition of Wapl, and stabilization of Cohesin on DNA. Our finding that Cohesin's ATPase activity is required for both Cohesin loading and Smc3 acetylation raises the possibility that cohesion establishment is directly coupled to the reaction in which Cohesin entraps DNA.
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Sister Chromatid Cohesion
Cold Spring Harbor Perspectives in Biology, 2012Co-Authors: Jan-michael Peters, Tomoko NishiyamaAbstract:During S phase, not only does DNA have to be replicated, but also newly synthesized DNA molecules have to be connected with each other. This sister chromatid cohesion is essential for the biorientation of chromosomes on the mitotic or meiotic spindle, and is thus an essential prerequisite for chromosome segregation. Cohesion is mediated by Cohesin complexes that are thought to embrace sister chromatids as large rings. Cohesin binds to DNA dynamically before DNA replication and is converted into a stably DNA-bound form during replication. This conversion requires acetylation of Cohesin, which in vertebrates leads to recruitment of sororin. Sororin antagonizes Wapl, a protein that is able to release Cohesin from DNA, presumably by opening the Cohesin ring. Inhibition of Wapl by sororin therefore “locks” Cohesin rings on DNA and allows them to maintain cohesion for long periods of time in mammalian oocytes, possibly for months or even years.
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Cohesin is required for higher order chromatin conformation at the imprinted igf2 h19 locus
PLOS Genetics, 2009Co-Authors: Raffaella Nativio, Kerstin S Wendt, Yoko Ito, Joanna E Huddleston, Santiago Uribelewis, Kathryn Woodfine, Christel Krueger, Wolf Reik, Jan-michael PetersAbstract:Cohesin is a chromatin-associated protein complex that mediates sister chromatid cohesion by connecting replicated DNA molecules. Cohesin also has important roles in gene regulation, but the mechanistic basis of this function is poorly understood. In mammalian genomes, Cohesin co-localizes with CCCTC binding factor (CTCF), a zinc finger protein implicated in multiple gene regulatory events. At the imprinted IGF2-H19 locus, CTCF plays an important role in organizing allele-specific higher-order chromatin conformation and functions as an enhancer blocking transcriptional insulator. Here we have used chromosome conformation capture (3C) assays and RNAi–mediated depletion of Cohesin to address whether Cohesin affects higher order chromatin conformation at the IGF2-H19 locus in human cells. Our data show that Cohesin has a critical role in maintaining CTCF–mediated chromatin conformation at the locus and that disruption of this conformation coincides with changes in IGF2 expression. We show that the Cohesin-dependent, higher-order chromatin conformation of the locus exists in both G1 and G2 phases of the cell cycle and is therefore independent of Cohesin's function in sister chromatid cohesion. We propose that Cohesin can mediate interactions between DNA molecules in cis to insulate genes through the formation of chromatin loops, analogous to the Cohesin mediated interaction with sister chromatids in trans to establish cohesion.
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sororin is required for stable binding of Cohesin to chromatin and for sister chromatid cohesion in interphase
Current Biology, 2007Co-Authors: Julia Schmitz, Erwan Watrin, Peter Lenart, Karl Mechtler, Jan-michael PetersAbstract:Sister chromatid cohesion depends on Cohesin [1-3]. Cohesin associates with chromatin dynamically throughout interphase [4]. During DNA replication, Cohesin establishes cohesion [5], and this process coincides with the generation of a Cohesin subpopulation that is more stably bound to chromatin [4]. In mitosis, Cohesin is removed from chromosomes, enabling sister chromatid separation [6]. How Cohesin associates with chromatin and establishes cohesion is poorly understood. By searching for proteins that are associated with chromatin-bound Cohesin, we have identified sororin, a protein that was known to be required for cohesion [7]. To obtain further insight into sororin's function, we have addressed when during the cell cycle sororin is required for cohesion. We show that sororin is dispensable for the association of Cohesin with chromatin but that sororin is essential for proper cohesion during G2 phase. Like Cohesin, sororin is also needed for efficient repair of DNA double-strand breaks in G2. Finally, sororin is required for the presence of normal amounts of the stably chromatin-bound Cohesin population in G2. Our data indicate that sororin interacts with chromatin-bound Cohesin and functions during the establishment or maintenance of cohesion in S or G2 phase, respectively.
Stéphanie Vazquez - One of the best experts on this subject based on the ideXlab platform.
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a second wpl1 anti cohesion pathway requires dephosphorylation of fission yeast kleisin rad21 by pp4
The EMBO Journal, 2017Co-Authors: Adrien Birot, Jean-paul Javerzat, Karen Eguienta, Stéphanie Vazquez, Karl Ekwall, Stéphane Claverol, Marc Bonneu, Sabine VaurAbstract:Abstract Cohesin mediates sister chromatid cohesion which is essential for chromosome segregation and repair. Sister chromatid cohesion requires an acetyl‐transferase (Eso1 in fission yeast) counteracting Wpl1, promoting Cohesin release from DNA. We report here that Wpl1 anti‐cohesion function includes an additional mechanism. A genetic screen uncovered that Protein Phosphatase 4 (PP4) mutants allowed cell survival in the complete absence of Eso1. PP4 co‐immunoprecipitated Wpl1 and Cohesin and Wpl1 triggered Rad21 de‐phosphorylation in a PP4‐dependent manner. Relevant residues were identified and mapped within the central domain of Rad21. Phospho‐mimicking alleles dampened Wpl1 anti‐cohesion activity, while alanine mutants were neutral indicating that Rad21 phosphorylation would shelter Cohesin from Wpl1 unless erased by PP4. Experiments in post‐replicative cells lacking Eso1 revealed two Cohesin populations. Type 1 was released from DNA by Wpl1 in a PP4‐independent manner. Type 2 Cohesin, however, remained DNA‐bound and lost its cohesiveness in a manner depending on Wpl1‐ and PP4‐mediated Rad21 de‐phosphorylation. These results reveal that Wpl1 antagonizes sister chromatid cohesion by a novel pathway regulated by the phosphorylation status of the Cohesin kleisin subunit.
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A second Wpl1 anti‐cohesion pathway requires dephosphorylation of fission yeast kleisin Rad21 by PP4
The EMBO journal, 2017Co-Authors: Adrien Birot, Jean-paul Javerzat, Karen Eguienta, Stéphanie Vazquez, Karl Ekwall, Stéphane Claverol, Marc Bonneu, Sabine VaurAbstract:Abstract Cohesin mediates sister chromatid cohesion which is essential for chromosome segregation and repair. Sister chromatid cohesion requires an acetyl‐transferase (Eso1 in fission yeast) counteracting Wpl1, promoting Cohesin release from DNA. We report here that Wpl1 anti‐cohesion function includes an additional mechanism. A genetic screen uncovered that Protein Phosphatase 4 (PP4) mutants allowed cell survival in the complete absence of Eso1. PP4 co‐immunoprecipitated Wpl1 and Cohesin and Wpl1 triggered Rad21 de‐phosphorylation in a PP4‐dependent manner. Relevant residues were identified and mapped within the central domain of Rad21. Phospho‐mimicking alleles dampened Wpl1 anti‐cohesion activity, while alanine mutants were neutral indicating that Rad21 phosphorylation would shelter Cohesin from Wpl1 unless erased by PP4. Experiments in post‐replicative cells lacking Eso1 revealed two Cohesin populations. Type 1 was released from DNA by Wpl1 in a PP4‐independent manner. Type 2 Cohesin, however, remained DNA‐bound and lost its cohesiveness in a manner depending on Wpl1‐ and PP4‐mediated Rad21 de‐phosphorylation. These results reveal that Wpl1 antagonizes sister chromatid cohesion by a novel pathway regulated by the phosphorylation status of the Cohesin kleisin subunit.
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A second Wpl1 anti‐cohesion pathway requires dephosphorylation of fission yeast kleisin Rad21 by PP 4
EMBO Journal, 2017Co-Authors: Adrien Birot, Jean-paul Javerzat, Karen Eguienta, Sabine Vaur, Stéphanie Vazquez, Karl Ekwall, Stéphane Claverol, Marc Bonneu, Jean‐paul JaverzatAbstract:Cohesin mediates sister chromatid cohesion which is essential for chromosome segregation and repair. Sister chromatid cohesion requires an acetyl-transferase (Eso1 in fission yeast) counteracting Wpl1, promoting Cohesin release from DNA We report here that Wpl1 anti-cohesion function includes an additional mechanism. A genetic screen uncovered that Protein Phosphatase 4 (PP4) mutants allowed cell survival in the complete absence of Eso1. PP4 co-immunoprecipitated Wpl1 and Cohesin and Wpl1 triggered Rad21 de-phosphorylation in a PP4-dependent manner. Relevant residues were identified and mapped within the central domain of Rad21. Phospho-mimicking alleles dampened Wpl1 anti-cohesion activity, while alanine mutants were neutral indicating that Rad21 phosphorylation would shelter Cohesin from Wpl1 unless erased by PP4. Experiments in post-replicative cells lacking Eso1 revealed two Cohesin populations. Type 1 was released from DNA by Wpl1 in a PP4-independent manner. Type 2 Cohesin, however, remained DNA-bound and lost its cohesiveness in a manner depending on Wpl1- and PP4-mediated Rad21 de-phosphorylation. These results reveal that Wpl1 antagonizes sister chromatid cohesion by a novel pathway regulated by the phosphorylation status of the Cohesin kleisin subunit.
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Pds5 promotes Cohesin acetylation and stable Cohesin–chromosome interaction
EMBO reports, 2012Co-Authors: Sabine Vaur, Stéphanie Vazquez, Amélie Feytout, Jean-paul JaverzatAbstract:Pds5 and Wpl1 act as anti-establishment factors preventing sister-chromatid cohesion until counteracted in S-phase by the Cohesin acetyl-transferase Eso1. However, Pds5 is also required to maintain sister-chromatid cohesion in G2. Here, we show that Pds5 is essential for Cohesin acetylation by Eso1 and ensures the maintenance of cohesion by promoting a stable Cohesin interaction with replicated chromosomes. The latter requires Eso1 only in the presence of Wapl, indicating that Cohesin stabilization relies on Eso1 only to neutralize the anti-establishment activity. We suggest that Eso1 requires Pds5 to counteract anti-establishment. This allows both cohesion establishment and Pds5-dependent stable Cohesin binding to chromosomes.
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psm3 acetylation on conserved lysine residues is dispensable for viability in fission yeast but contributes to eso1 mediated sister chromatid cohesion by antagonizing wpl1
Molecular and Cellular Biology, 2011Co-Authors: Amélie Feytout, Sylvie Genier, Sabine Vaur, Stéphanie Vazquez, Jean-paul JaverzatAbstract:: In budding yeast and humans, cohesion establishment during S phase requires the acetyltransferase Eco1/Esco1-2, which acetylates the Cohesin subunit Smc3 on two conserved lysine residues. Whether Smc3 is the sole Eco1/Esco1-2 effector and how Smc3 acetylation promotes cohesion are unknown. In fission yeast (Schizosaccharomyces pombe), as in humans, Cohesin binding to G(1) chromosomes is dynamic and the unloading reaction is stimulated by Wpl1 (human ortholog, Wapl). During S phase, a subpopulation of Cohesin becomes stably bound to chromatin in an Eso1 (fission yeast Eco1/Esco1-2)-dependent manner. Cohesin stabilization occurs unevenly along chromosomes. Cohesin remains largely labile at the rDNA repeats but binds mostly in the stable mode to pericentromere regions. This pattern is largely unchanged in eso1Δ wpl1Δ cells, and cohesion is unaffected, indicating that the main Eso1 role is counteracting Wpl1. A mutant of Psm3 (fission yeast Smc3) that mimics its acetylated state renders Cohesin less sensitive to Wpl1-dependent unloading and partially bypasses the Eso1 requirement but cannot generate the stable mode of Cohesin binding in the absence of Eso1. Conversely, nonacetylatable Psm3 reduces the stable Cohesin fraction and affects cohesion in a Wpl1-dependent manner, but cells are viable. We propose that Psm3 acetylation contributes to Eso1 counteracting of Wpl1 to secure stable Cohesin interaction with postreplicative chromosomes but that it is not the sole molecular event by which this occurs.
Adrien Birot - One of the best experts on this subject based on the ideXlab platform.
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a second wpl1 anti cohesion pathway requires dephosphorylation of fission yeast kleisin rad21 by pp4
The EMBO Journal, 2017Co-Authors: Adrien Birot, Jean-paul Javerzat, Karen Eguienta, Stéphanie Vazquez, Karl Ekwall, Stéphane Claverol, Marc Bonneu, Sabine VaurAbstract:Abstract Cohesin mediates sister chromatid cohesion which is essential for chromosome segregation and repair. Sister chromatid cohesion requires an acetyl‐transferase (Eso1 in fission yeast) counteracting Wpl1, promoting Cohesin release from DNA. We report here that Wpl1 anti‐cohesion function includes an additional mechanism. A genetic screen uncovered that Protein Phosphatase 4 (PP4) mutants allowed cell survival in the complete absence of Eso1. PP4 co‐immunoprecipitated Wpl1 and Cohesin and Wpl1 triggered Rad21 de‐phosphorylation in a PP4‐dependent manner. Relevant residues were identified and mapped within the central domain of Rad21. Phospho‐mimicking alleles dampened Wpl1 anti‐cohesion activity, while alanine mutants were neutral indicating that Rad21 phosphorylation would shelter Cohesin from Wpl1 unless erased by PP4. Experiments in post‐replicative cells lacking Eso1 revealed two Cohesin populations. Type 1 was released from DNA by Wpl1 in a PP4‐independent manner. Type 2 Cohesin, however, remained DNA‐bound and lost its cohesiveness in a manner depending on Wpl1‐ and PP4‐mediated Rad21 de‐phosphorylation. These results reveal that Wpl1 antagonizes sister chromatid cohesion by a novel pathway regulated by the phosphorylation status of the Cohesin kleisin subunit.
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A second Wpl1 anti‐cohesion pathway requires dephosphorylation of fission yeast kleisin Rad21 by PP4
The EMBO journal, 2017Co-Authors: Adrien Birot, Jean-paul Javerzat, Karen Eguienta, Stéphanie Vazquez, Karl Ekwall, Stéphane Claverol, Marc Bonneu, Sabine VaurAbstract:Abstract Cohesin mediates sister chromatid cohesion which is essential for chromosome segregation and repair. Sister chromatid cohesion requires an acetyl‐transferase (Eso1 in fission yeast) counteracting Wpl1, promoting Cohesin release from DNA. We report here that Wpl1 anti‐cohesion function includes an additional mechanism. A genetic screen uncovered that Protein Phosphatase 4 (PP4) mutants allowed cell survival in the complete absence of Eso1. PP4 co‐immunoprecipitated Wpl1 and Cohesin and Wpl1 triggered Rad21 de‐phosphorylation in a PP4‐dependent manner. Relevant residues were identified and mapped within the central domain of Rad21. Phospho‐mimicking alleles dampened Wpl1 anti‐cohesion activity, while alanine mutants were neutral indicating that Rad21 phosphorylation would shelter Cohesin from Wpl1 unless erased by PP4. Experiments in post‐replicative cells lacking Eso1 revealed two Cohesin populations. Type 1 was released from DNA by Wpl1 in a PP4‐independent manner. Type 2 Cohesin, however, remained DNA‐bound and lost its cohesiveness in a manner depending on Wpl1‐ and PP4‐mediated Rad21 de‐phosphorylation. These results reveal that Wpl1 antagonizes sister chromatid cohesion by a novel pathway regulated by the phosphorylation status of the Cohesin kleisin subunit.
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A second Wpl1 anti‐cohesion pathway requires dephosphorylation of fission yeast kleisin Rad21 by PP 4
EMBO Journal, 2017Co-Authors: Adrien Birot, Jean-paul Javerzat, Karen Eguienta, Sabine Vaur, Stéphanie Vazquez, Karl Ekwall, Stéphane Claverol, Marc Bonneu, Jean‐paul JaverzatAbstract:Cohesin mediates sister chromatid cohesion which is essential for chromosome segregation and repair. Sister chromatid cohesion requires an acetyl-transferase (Eso1 in fission yeast) counteracting Wpl1, promoting Cohesin release from DNA We report here that Wpl1 anti-cohesion function includes an additional mechanism. A genetic screen uncovered that Protein Phosphatase 4 (PP4) mutants allowed cell survival in the complete absence of Eso1. PP4 co-immunoprecipitated Wpl1 and Cohesin and Wpl1 triggered Rad21 de-phosphorylation in a PP4-dependent manner. Relevant residues were identified and mapped within the central domain of Rad21. Phospho-mimicking alleles dampened Wpl1 anti-cohesion activity, while alanine mutants were neutral indicating that Rad21 phosphorylation would shelter Cohesin from Wpl1 unless erased by PP4. Experiments in post-replicative cells lacking Eso1 revealed two Cohesin populations. Type 1 was released from DNA by Wpl1 in a PP4-independent manner. Type 2 Cohesin, however, remained DNA-bound and lost its cohesiveness in a manner depending on Wpl1- and PP4-mediated Rad21 de-phosphorylation. These results reveal that Wpl1 antagonizes sister chromatid cohesion by a novel pathway regulated by the phosphorylation status of the Cohesin kleisin subunit.